A novel chemokine biomarker to distinguish active tuberculosis from latent tuberculosis: a cohort study

Abstract

Summary Background Interferon-γ release assays (IGRAs), which are widely used to diagnose tuberculosis (TB), cannot effectively discriminate latent TB infection (LTBI) from active TB (ATB). This study aimed to identify potential antigen-specific biomarkers for differentiating LTBI cases from ATB cases. Methods Ongoing recruitment was conducted of individuals meeting study inclusion criteria at Beijing Chest Hospital from May 2020 to April 2022; 208 participants were enrolled and assigned to three groups: HC (60 healthy controls), LTBI (52 subjects with LTBI) and ATB (96 ATB patients). After participants were assigned to the discovery cohort (20 or 21 subjects/group), all others were assigned to the verification cohort. Discovery cohort blood levels of 40 chemokines were measured using Luminex assays to identify chemokines that could be used to discriminate LTBI cases from ATB cases; candidate biomarkers were verified using enzyme-linked immunosorbent assay-based testing of validation cohort samples. Results Luminex results revealed highest ATB group levels of numerous cytokines, growth factors and chemokines. Receiving operating characteristic curve-based analysis of 40 biomarkers revealed CCL8 (AUC = 0.890) and CXCL9 (AUC = 0.883) effectively discriminated between LTBI and TB cases; greatest diagnostic efficiency was obtained using both markers together (AUC = 0.929). Interpretation of CCL8 and CXCL9 levels for validation cohort IGRA-positive subjects (based on a 0.658-ng/ml cutoff) revealed ATB group CCL8-based sensitivity and specificity rates approaching 90.79% and 100.00%, respectively. Conclusion TB-specific chemokines hold promise as ATB diagnostic biomarkers. Additional laboratory confirmation is needed to establish whether CCL8-based assays can differentiate between ATB and LTBI cases, especially for bacteriologically unconfirmed TB cases.